We propose a wide ranging program of research on the molecular bases of the nature and specificity of nucleic acid-protein interactions involved in the function of physiologically-relevent genome systems. We plan to complete our examination of the equilibrium and kinetic interactions of bacteriophage T4-coded gene 32 protein with various DNA and RNA substrates. In these studies we will stress the development of binding specificity as a consequence of cooperativity of binding, and the kinetics whereby particular single-stranded binding proteins may, or may not, bring about the "melting" of double-stranded DNA systems. T4-coded gene 32 protein is a particularly useful probe for such studies, because the wild type protein itself will not bring about melting, but a proteolytically-"clipped" version of this protein will. In addition, we plan to continue our studies of the interaction of the various T4-coded proteins of the replication fork; examining how the various proteins influence the opening of the DNA double helix in replication formation, the contributions which various proteins make to the processivity of movement of the polymerase down the fork, and extent to which ATP (or GTP) cleavage is required to effect helix-destabilizing and polymerase translocation processes. In addition, we will continue our studies of the elongation and termination processes in mRNA synthesis by E. coli DNA-dependent RNA polymerase. We have isolated a specific piece of the lambda genome, which we are using in trascription studies to examine the movement of RNA polymerase through a "real" DNA genome, and the mechanisms whereby termination of this transcription process is brought about. In particular, we are investigating rho-dependent transcription termination, both directly on the above specific system and by examining the physical biochemical interactions between rho protein and various nucleic acid substrates. The emphasis throughout these studies will continue to be on the elucidation of the general principles (at the molecular level) of genome regulatory systems in prokaryotes and eukaryotes.